ANTIHYPERTENSIVE AND CARDIOVASCULAR EFFECTS OF A NEW POTASSIUM CHANNEL OPENER, TCV-295, IN RATS AND DOGS

The antihypertensive and cardiovascular properties of a new potassium channel opener, TCV-295, were studied in rats and dogs. In conscious, spontaneously hypertensive rats (SHR), TCV-295 (0.03-1 mg/kg orally, p .o.) reduced blood pressure (BP) dose dependently with slow onset of a ction. The antihypertensive effects induced by TCV-295 lasted much lon ger than those of levcromakalim and nisoldipine, and the reflex tachyc ardia is evoked was less marked than that evoked by these drugs as com pared at doses showing similar maximal hypotensive effects. Gilbenclam ide (30 mg/kg intravenously, i.v.) inhibited the TCV-205-induced BP de crease in anesthetized rats. In a 4-week chronic dosing study in SHR, TCV-295 (0.3 mg/kg/day p.o.) produced neither potentiation nor toleran ce to its antihypertensive action and no rebound hypertension occurred when drug treatment was discontinued. In anesthetized normotensive do gs, TCV-295 (4.5 mu g/kg/min i.v.) induced BP reductions accompanied b y reductions in systemic vascular resistance. TCV-295 also reduced res istances of the coronary, vertebral, mesenteric, and renal vascular be ds, and the most marked effect was observed in the coronary vasculatur e. Myocardial O-2 consumption was reduced by TCV-295, possibly owing t o afterload decrease. These results suggest that TCV-295 has a desirab le profile for an antihypertensive agent.